@phdthesis{oai:sucra.repo.nii.ac.jp:00010375,
 author = {CHAYON, GOSWAMI},
 month = {},
 note = {x, 66 p., Motilin and ghrelin constitute a peptide family, and these hormones are important for the regulation of gastrointestinal motility. In this study, we examined the effect of motilin and ghrelin on gastric acid secretion in anesthetized suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. We first established a gastric lumen-perfusion system in the suncus and confirmed that intravenous (i.v.) administration of histamine (1 mg/kg BW) stimulated acid secretion. Motilin (0.1, 1.0, and 10 μg/kg BW) stimulated the acid output in a dose-dependent manner in suncus, whereas ghrelin (0.1, 1.0, and 10 μg/kg BW) alone did not induce acid output. Furthermore, in comparison with the vehicle administration, the co-administration of low-dose (1 μg/kg BW) motilin and ghrelin significantly stimulated gastric acid secretion, whereas either motilin (1 μg/kg BW) or ghrelin (1 μg/kg BW) alone did not significantly induce gastric acid secretion. This indicates an additive role of ghrelin in motilin-induced gastric acid secretion. We then investigated the pathways of motilin/motilin and ghrelin-stimulated acid secretion using receptor antagonists. Treatment with YM 022 (a CCK-B receptor antagonist) and atropine (a muscarinic acetylcholine receptor antagonist) had no effect on motilin or motilin-ghrelin co-administration-induced acid output. In contrast, famotidine (a histamine H2 receptor antagonist) completely inhibited motilin-stimulated acid secretion and co-administration of motilin and ghrelin induced gastric acid output. This is the first report demonstrating that motilin stimulates gastric secretion in mammals. By using the above mentioned gastric lumen-perfusion system, we also found that the intravenous administration of carbachol and motilin (0.1, 1.0, and 10 μg/kg BW) stimulated pepsinogen secretion, the latter in a dose-dependent manner, whereas ghrelin had no effect. We then investigated the pathways of motilin-induced pepsinogen secretion using acetylcholine receptor antagonists. Treatment with atropine, a muscarinic acetylcholine receptor antagonist, completely inhibited both carbachol and motilin-induced pepsinogen secretion. Motilin-induced pepsinogen secretion was also observed in the vagotomized suncus. Our results suggest that motilin stimulates gastric acid secretion via the histamine-mediated pathway and also stimulates pepsinogen secretion through a cholinergic pathway in suncus., ABSTRACT　　　I
ACKNOWLEDGEMENTS　　　III
TABLE OF CONTENTS　　　V
LIST OF FIGURES　　　IX
Chapter 1: General Introduction and Objectives　　　1
1.1. Research background　　　1
1.1.1. Gastric acid secretion and its role in gastric acid secretion　　　1
1.1.2. Pepsinogen secretion and its role in gastric acid secretion　　　1
1.1.3. Motilin　　　2
1.1.4. Ghrelin　　　2
1.1.5. Similar properties between motilin and ghrelin　　　3
1.1.6. House musk shrew (Suncus murinus)　　　4
1.2. Hypothesis　　　5
1.3. General objectives　　　5
Chapter 2: Motilin stimulates gastric acid secretion in co-ordination with ghrelin in Suncus murinus　　　6
2.1. Introduction　　　6
2.1.1. Gastric acid secretion mechanism　　　6
2.1.2. Motilin and ghrelin, and their functions in relation to gastric acid secretion　　　6
2.1.3. Advantages of suncus for studying gastrointestinal physiology including gastric acid experiment　　　7
2.2. Materials and Methods　　　9
2.2.1. Animals　　　9
2.2.2. Drugs　　　9
2.2.3. Determination of gastric acid output by an intragastric perfusion experimental system　　　10
2.2.4. Measurement of pH and amount of gastric acid　　　11
2.2.5. Experimental protocols　　　11
2.2.6. Statistical analyses　　　12
2.3. Results　　　13
2.3.1. Effect of ghrelin, motilin, and co-administration of motilin and ghrelin on gastric acid secretion　　　13
2.3.2. Effect of famotidine on motilin, and co-administration of motilin and ghrelin-stimulated gastric acid secretion　　　14
2.3.3. Effect of YM 022 on gastric acid secretion stimulated by motilin, and co-administration of motilin and ghrelin　　　15
2.3.4. Effect of atropine on motilin, and co-administration of motilin and ghrelin-stimulated gastric acid secretion　　　15
2.4. Discussion　　　17
2.4.1. Suncus for gastric acid secretion study　　　17
2.4.2. Motilin but not ghrelin stimulate gastric acid secretion　　　17
2.4.3. Physiological importance of motilin-induced gastric acid secretion　　　18
2.4.4. Regulatory mechanism of motilin-induced gastric acid secretion　　　19
2.5. Summary　　　21
Chapter 3: Motilin stimulates pepsinogen secretion in Suncus murinus　　　22
3.1. Introduction　　　22
3.1.1. Regulatory mechanism of pepsinogen secretion　　　22
3.1.2. Motilin and ghrelin, and their functions in gastrointestinal tract　　　23
3.1.3. Advantages of suncus as an experimental animal for pepsinogen secretion study　　　23
3.1.4. Gastric contraction and pepsinogen secretion　　　24
3.2. Materials and Methods　　　25
3.2.1. Animals　　　25
3.2.2. Drugs　　　25
3.2.3. Determination of pepsin output using an intragastric perfusion experimental system　　　25
3.2.4. Vagotomy　　　26
3.2.5. Pepsin measurement　　　27
3.2.6. Experimental protocols　　　27
3.2.7. Statistical analyses　　　28
3.3. Results　　　29
3.3.1. Establishment of a perfusion system for pepsinogen measurement in suncus　　　29
3.3.2. Effects of motilin on pepsinogen secretion　　　29
3.3.3. Effects of ghrelin on pepsinogen secretion　　　29
3.3.4. Effect of atropine on motilin-induced pepsinogen secretion　　　30
3.3.5. Effect of vagotomy on motilin-induced pepsinogen secretion　　　30
3.3.6. Effect of motilin and histamine on both pH and pepsinogen secretion　　　31
3.3.7. Effect of co-administration of motilin and ghrelin on pepsinogen secretion　　　31
3.4. Discussion　　　32
3.4.1. Suncus as a suitable model animal for pepsinogen secretion experiments　　　32
3.4.2. Motilin-induced pepsinogen secretion and its physiological importance　　　32
3.4.3. Motilin but not ghrelin stimulates pepsinogen secretion through cholinergic pathway　　　34
3.5. Summary　　　35
CONCLUSIONS　　　36
ABBREVIATIONS　　　37
REFERENCES　　　38
FIGURES　　　49, 指導教員 : 坂井貴文, text, application/pdf},
 school = {埼玉大学},
 title = {The regulatory mechanism of motilin induced gastric acid and pepsinogen secretion in Suncus murinus},
 year = {2015},
 yomi = {チャヨン, グッサミ}
}